tbuckley/cabot-search huggingface dataset:
Genomic epidemiology of SARS-CoV-2 infections in The Gambia: an analysis of routinely collected surveillance data between March, 2020, and January, 2022
Authors: Abdoulie Kanteh, Haruna S Jallow, Jarra Manneh, Bakary Sanyang, Mariama A Kujabi, Sainabou Laye Ndure, Sheikh Jarju, Alhagie Papa Sey, Dabiri Damilare K, Yaya Bah, Sana Sambou, Gibril Jarju, Buba Manjang, Abubacarr Jagne, Sheikh Omar Bittaye, Mustapha Bittaye, Karen Forrest, Desta Alamerew Tiruneh, Ahmadou Lamin Samateh, Sheriffo Jagne, Stéphane Hué, Nuredin Mohammed, Alfred Amambua-Ngwa, Beate Kampmann, Umberto D'Alessandro, Thushan I de Silva, Anna Roca, Abdul Karim Sesay
Journal: The Lancet Global Health (2023)
Leveraging massively parallel reporter assays for evolutionary questions
Authors: Irene Gallego Romero, Amanda J. Lea
Journal: Genome biology (2023)

Abstract A long-standing goal of evolutionary biology is to decode how gene regulation contributes to organismal diversity. Doing so is challenging because it is hard to predict function from non-coding sequence and to perform molecular research with non-model taxa. Massively parallel reporter assays (MPRAs) enable the testing of thousands to millions of sequences for regulatory activity simultaneously. Here, we discuss the execution, advantages, and limitations of MPRAs, with a focus on evolutionary questions. We propose solutions for extending MPRAs to rare taxa and those with limited genomic resources, and we underscore MPRA’s broad potential for driving genome-scale, functional studies across organisms.
Preclinical models of prostate cancer — modelling androgen dependency and castration resistance in vitro, ex vivo and in vivo
Authors: Lucas Germain, Camille Lafront, Virginie Paquette, Bertrand Neveu, Jean-Sébastien Paquette, Frédéric Pouliot, Étienne Audet-Walsh
Journal: Nature Reviews Urology (2023)
Ultra-low-coverage genome-wide association study—insights into gestational age using 17,844 embryo samples with preimplantation genetic testing
Authors: Shumin Li, Bin Yan, Thomas K. T. Li, Jianliang Lu, Yifan Gu, Yueqiu Tan, Fei Gong, Tak-Wah Lam, Pingyuan Xie, Yuexuan Wang, Ge Lin, Ruibang Luo
Journal: Genome Medicine (2023)

Abstract Background Very low-coverage (0.1 to 1×) whole genome sequencing (WGS) has become a promising and affordable approach to discover genomic variants of human populations for genome-wide association study (GWAS). To support genetic screening using preimplantation genetic testing (PGT) in a large population, the sequencing coverage goes below 0.1× to an ultra-low level. However, the feasibility and effectiveness of ultra-low-coverage WGS (ulcWGS) for GWAS remains undetermined. Methods We built a pipeline to carry out analysis of ulcWGS data for GWAS. To examine its effectiveness, we benchmarked the accuracy of genotype imputation at the combination of different coverages below 0.1× and sample sizes from 2000 to 16,000, using 17,844 embryo PGT samples with approximately 0.04× average coverage and the standard Chinese sample HG005 with known genotypes. We then applied the imputed genotypes of 1744 transferred embryos who have gestational ages and complete follow-up records to GWAS. Results The accuracy of genotype imputation under ultra-low coverage can be improved by increasing the sample size and applying a set of filters. From 1744 born embryos, we identified 11 genomic risk loci associated with gestational ages and 166 genes mapped to these loci according to positional, expression quantitative trait locus, and chromatin interaction strategies. Among these mapped genes, CRHBP , ICAM1 , and OXTR were more frequently reported as preterm birth related. By joint analysis of gene expression data from previous studies, we constructed interrelationships of mainly CRHBP , ICAM1 , PLAGL1 , DNMT1 , CNTLN , DKK1 , and EGR2 with preterm birth, infant disease, and breast cancer. Conclusions This study not only demonstrates that ulcWGS could achieve relatively high accuracy of adequate genotype imputation and is capable of GWAS, but also provides insights into the associations between gestational age and genetic variations of the fetal embryos from Chinese population.
Ultrafast Miniature Robotic Swimmers with Upstream Motility
Authors: Yibin Wang, Hui Chen, Junhui Law, Xingzhou Du, Jiangfan Yu
Journal: Cyborg and Bionic Systems (2023)

With the development of materials science and micro-nano fabrication techniques, miniature soft robots at millimeter or submillimeter size can be manufactured and actuated remotely. The small-scaled robots have the unique capability to access hard-to-reach regions in the human body in a noninvasive manner. To date, it is still challenging for miniature robots to accurately move in the diverse and dynamic environments in the human body (e.g., in blood flow). To effectively locomote in the vascular system, miniature swimmers with upstream swimming capability are required. Herein, we design and fabricate a miniature robotic swimmer capable of performing ultrafast swimming in a fluidic environment. The maximum velocity of the swimmer in water is 30 cm/s, which is 60 body lengths. Moreover, in a tubular environment, the swimmer can still obtain a swimming velocity of 17 cm/s. The swimmer can also perform upstream swimming in a tubular environment with a velocity of 5 cm/s when the flow speed is 10 cm/s. The ultrasound-guided navigation of the swimmer in a phantom mimicking a blood vessel is also realized. This work gives insight into the design of agile undulatory milliswimmers for future biomedical applications.
Correction: Disturbances in microbial skin recolonization and cutaneous immune response following allogeneic stem cell transfer
Authors: Nadine Bayer, Bela Hausmann, Ram Vinay Pandey, Florian Deckert, Laura-Marie Gail, Johanna Strobl, Petra Pjevac, Christoph Krall, Luisa Unterluggauer, Anna Redl, Victoria Bachmayr, Lisa Kleissl, Marion Nehr, Rasmus Kirkegaard, Athanasios Makristathis, Martin L. Watzenboeck, Robert Nica, Clement Staud, Lukas Hammerl, Philipp Wohlfarth, Rupert C. Ecker, Sylvia Knapp, Werner Rabitsch, David Berry, Georg Stary
Journal: Leukemia (2023)
A human antibody epitope map of Pfs230D1 derived from analysis of individuals vaccinated with a malaria transmission-blocking vaccine
Authors: Wai Kwan Tang, Camila H. Coelho, Kazutoyo Miura, Bergeline C. Nguemwo Tentokam, Nichole D. Salinas, David L. Narum, Sara A. Healy, Issaka Sagara, Carole A. Long, Patrick E. Duffy, Niraj H. Tolia
Journal: Immunity (2023)
Pregnancy-induced changes to the gut microbiota drive macrophage pyroptosis and exacerbate septic inflammation
Authors: Xia Chen, Rong Wu, Lei Li, Yunong Zeng, Jingrui Chen, Mingyuan Wei, Yinglin Feng, Guiming Chen, Yuhang Wang, Lizhen Lin, Haihua Luo, Ali Chen, Zhenhua Zeng, Fangjie He, Yang Bai, Siyou Zhang, Yubing Han, Zhang Wang, Xiaoshan Zhao, Wei Xiao, Yong Jiang, Shenhai Gong
Journal: Immunity (2023)
Highly potent, naturally acquired human monoclonal antibodies against Pfs48/45 block Plasmodium falciparum transmission to mosquitoes
Authors: Amanda Fabra-García, Sophia Hailemariam, Roos M. de Jong, Kirsten Janssen, Karina Teelen, Marga van de Vegte-Bolmer, Geert-Jan van Gemert, Danton Ivanochko, Anthony Semesi, Brandon McLeod, Martijn W. Vos, Marloes H.C. de Bruijni, Judith M. Bolscher, Marta Szabat, Stefanie Vogt, Lucas Kraft, Sherie Duncan, Moses R. Kamya, Margaret E. Feeney, Prasanna Jagannathan, Bryan Greenhouse, Koen J. Dechering, Robert W. Sauerwein, C. Richter King, Randall S. MacGill, Teun Bousema, Jean-Philippe Julien, Matthijs M. Jore
Journal: Immunity (2023)

Malaria transmission-blocking vaccines (TBVs) aim to induce antibodies that interrupt malaria parasite development in the mosquito, thereby blocking onward transmission, and provide a much-needed tool for malaria control and elimination. The parasite surface protein Pfs48/45 is a leading TBV candidate. Here, we isolated and characterized a panel of 81 human Pfs48/45-specific monoclonal antibodies (mAbs) from donors naturally exposed to Plasmodium parasites. Genetically diverse mAbs against each of the three domains (D1–D3) of Pfs48/45 were identified. The most potent mAbs targeted D1 and D3 and achieved >80% transmission-reducing activity in standard membrane-feeding assays, at 10 and 2 μg/mL, respectively. Co-crystal structures of D3 in complex with four different mAbs delineated two conserved protective epitopes. Altogether, these Pfs48/45-specific human mAbs provide important insight into protective and non-protective epitopes that can further our understanding of transmission and inform the design of refined malaria transmission-blocking vaccine candidates.
Principles of regulatory T cell function
Authors: Stanislav Dikiy, Alexander Y. Rudensky
Journal: Immunity (2023)

Regulatory T (Treg) cells represent a distinct lineage of cells of the adaptive immune system indispensable for forestalling fatal autoimmune and inflammatory pathologies. The role of Treg cells as principal guardians of the immune system can be attributed to their ability to restrain all currently recognized major types of inflammatory responses through modulating the activity of a wide range of cells of the innate and adaptive immune system. This broad purview over immunity and inflammation is afforded by the multiple modes of action Treg cells exert upon their diverse molecular and cellular targets. Beyond the suppression of autoimmunity for which they were originally recognized, Treg cells have been implicated in tissue maintenance, repair, and regeneration under physiologic and pathologic conditions. Herein, we discuss the current and emerging understanding of Treg cell effector mechanisms in the context of the basic properties of Treg cells that endow them with such functional versatility.
Potent transmission-blocking monoclonal antibodies from naturally exposed individuals target a conserved epitope on Plasmodium falciparum Pfs230
Authors: Danton Ivanochko, Amanda Fabra-García, Karina Teelen, Marga van de Vegte-Bolmer, Geert-Jan van Gemert, Jocelyn Newton, Anthony Semesi, Marloes de Bruijni, Judith Bolscher, Jordache Ramjith, Marta Szabat, Stefanie Vogt, Lucas Kraft, Sherie Duncan, Shwu-Maan Lee, Moses R. Kamya, Margaret E. Feeney, Prasanna Jagannathan, Bryan Greenhouse, Robert W. Sauerwein, C. Richter King, Randall S. MacGill, Teun Bousema, Matthijs M. Jore, Jean-Philippe Julien
Journal: Immunity (2023)

Pfs230 is essential for Plasmodium falciparum transmission to mosquitoes and is the protein targeted by the most advanced malaria-transmission-blocking vaccine candidate. Prior understanding of functional epitopes on Pfs230 is based on two monoclonal antibodies (mAbs) with moderate transmission-reducing activity (TRA), elicited from subunit immunization. Here, we screened the B cell repertoire of two naturally exposed individuals possessing serum TRA and identified five potent mAbs from sixteen Pfs230 domain-1-specific mAbs. Structures of three potent and three low-activity antibodies bound to Pfs230 domain 1 revealed four distinct epitopes. Highly potent mAbs from natural infection recognized a common conformational epitope that is highly conserved across P. falciparum field isolates, while antibodies with negligible TRA derived from natural infection or immunization recognized three distinct sites. Our study provides molecular blueprints describing P. falciparum TRA, informed by contrasting potent and non-functional epitopes elicited by natural exposure and vaccination.
A Cre-deleter specific for embryo-derived brain macrophages reveals distinct features of microglia and border macrophages
Authors: Simone Brioschi, Julia A. Belk, Vincent Peng, Martina Molgora, Patrick Fernandes Rodrigues, Khai M. Nguyen, Shoutang Wang, Siling Du, Wei-Le Wang, Gary E. Grajales-Reyes, Jennifer M. Ponce, Carla M. Yuede, Qingyun Li, John M. Baer, David G. DeNardo, Susan Gilfillan, Marina Cella, Ansuman T. Satpathy, Marco Colonna
Journal: Immunity (2023)
Clonal expansion of resident memory T cells in peripheral blood of patients with non-small cell lung cancer during immune checkpoint inhibitor treatment
Authors: Hyunsu Kim, Sehhoon Park, Kyoung-Yeon Han, Naeun Lee, Hyemin Kim, Hyun Ae Jung, Jong-Mu Sun, Jin Seok Ahn, Myung-Ju Ahn, Se-Hoon Lee, Woong-Yang Park
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background Immune checkpoint inhibitors (ICIs) are an essential treatment for non-small cell lung cancer (NSCLC). Currently, the tumor-related intrinsic factors in response to ICIs have mostly been elucidated in tissue samples. However, tissue immune status and changes in the immune microenvironment can also be reflected and monitored through peripheral blood. Methods Single-cell RNA and T cell receptor (scTCR) sequencing were conducted using peripheral blood mononuclear cells (PBMCs) from 60 patients with stage IV NSCLC. Those samples were prospectively acquired from patients treated with anti-PD(L)-1 therapy for advanced lung cancer. Based on the clinical outcomes, samples were classified as durable clinical benefit (DCB) and non-durable clinical benefit (NCB). The samples constituted paired longitudinal samples, consisting of pre-treatment and on-treatment. Additionally, PBMC samples from 60 healthy donors from the Asian Immune Diversity Atlas project were used as a control. Results The dynamic changes in major cell types between pre-treatment and on-treatment PBMCs were associated with an increase in proliferating T cells and NK cells in both DCB and NCB groups. Among T cell subtypes, effector memory CD8 + T cells (CD8 + T EM _GZMK_PDCD1) were increased after ICI treatment in both DCB and NCB. From the lineage trajectory analysis, effector memory CD8 + T cells resided at the bifurcation point, which has the potential to differentiate into lineages with precursor exhausted CD8 + T cells (CD8 + T CM cells) assumed to be related to the ICI response. From the scTCR-seq, effector memory CD8 + T cells along with T cells recognizing unknown antigen expanded and composed of novel clones skewed toward dysfunctional status, especially in on-treatment samples of the DCB group. The extent of immunophenotype conversion capabilities of the TCR with effector memory CD8 + T cells showed remarkable variation in the on-treatment sample in the DCB group. Conclusion A transitioning T cell subtype identified in PBMCs might be related to the prolonged ICI response. From our study, expansion of effector memory CD8 + T cells with novel TCRs in PBMCs after ICI treatment could contribute to a better clinical outcome in patients with NSCLC. This proof-of-concept research strengthens the use of non-invasive PBMCs in studying systemic changes of immune reactions related to the ICI treatment.
GLIS1 intervention enhances anti-PD1 therapy for hepatocellular carcinoma by targeting SGK1-STAT3-PD1 pathway
Authors: Dawei Rong, Yuliang Wang, Li Liu, Hengsong Cao, Tian Huang, Hanyuan Liu, Xiaopei Hao, Guangshun Sun, Guoqiang Sun, Zhiying Zheng, Junwei Kang, Yongxiang Xia, Ziyi Chen, Weiwei Tang, Xuehao Wang
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background GLI-similar 1 (GLIS1) is one of of Krüppel-like zinc finger proteins, which are either stimulators or inhibitors of genetic transcription. Nevertheless, its effects on T cell were elusive. Methods In this study, we intend to explore the effects of GLIS1 on modulating the anticancer potency of CD8 + T cells in hepatocellular carcinoma (HCC). The expression of GLIS1 in CD8 peripheral blood mononuclear cell and CD8 tumor-infiltrating lymphocytes of HCC tissues was validated by quantificational real-time-PCR and flow cytometry. The anticancer potency of CD8 + T cells with GLIS1 knock down was confirmed in C57BL/6 mouse model and HCC patient-derived xenograft mice model. GLIS1 –/– C57BL/6 mice was applied to explore the effects GLIS1 on tumor immune microenvironment. Chromatin immunoprecipitation and RNA transcriptome sequencing analysis were both performed in GLIS1-knock down of CD8 + T cells. Results GLIS1 was upregulated in exhausted CD8 + T cells in HCC. GLIS1 downregulation in CD8 + T cells repressed cancer development, elevated the infiltrate ability of CD8 + T cells, mitigated CD8 + T cell exhaustion and ameliorated the anti-PD1 reaction of CD8 + T cells in HCC. The causal link beneath this included transcriptional regulation of SGK1-STAT3-PD1 pathway by GLIS1, thereby maintaining the abundant PD1 expression on the surface of CD8 + T cells. Conclusion Our study revealed that GLIS1 promoted CD8 + T cell exhaustion in HCC through transcriptional regulating SGK1-STAT3-PD1 pathway. Downregulating the expression of GLIS1 in CD8 + T cells exerted an effect with anti-PD1 treatment synergistically, revealing a prospective method for HCC immune therapy.
Awareness of HIV, hepatitis B, hepatitis C, tuberculosis and COVID-19 in migrant students in the UK: a pilot survey from an Institute of Higher Education
Authors: Paul W Bird, Christopher W Holmes, Daniel Pan, Christopher A Martin, Manish Pareek, Mayuri Gogoi, Rominder Sandhu, Pamela Sargeant, Claire L McMurray, Rebecca F Baggaley, Laura B Nellums
Journal: Journal of Infection (2023)
Maternal helminth infection protects offspring from high-fat-diet-induced obesity through altered microbiota and SCFAs
Authors: Chien-Wen Su, Chih-Yu Chen, Tangyou Mao, Ning Chen, Nicholas Steudel, Lefei Jiao, Jinggang Lan, Alessio Fasano, W. Allan Walker, Hai Ning Shi
Journal: Cellular and Molecular Immunology (2023)
Electro-microenvironment modulated inhibition of endogenous biofilms by piezo implants for ultrasound-localized intestinal perforation disinfection
Authors: Xing Zhao, Li-Ya Wang, Chun-Yan Tang, Kai Li, Yan-Hao Huang, Yan-Ran Duan, Shu-Ting Zhang, Kai Ke, Bai-Hai Su, Wei Yang
Journal: Biomaterials (2023)
Society News
Journal: Neuro-Oncology (2023)

Journal Article Society News Get access Neuro-Oncology, Volume 25, Issue 2, February 2023, Page 431, https://doi.org/10.1093/neuonc/noad010 Published: 14 February 2023 Article history Corrected and typeset: 14 February 2023 Published: 14 February 2023
Stramonium Intoxication
Authors: John M. Gowdy
Journal: JAMA (1972)

Asthma powders, designed to be burned and inhaled, produce hallucinations when taken by mouth. They are popular with the younger set because of their availability and lack of legal restrictions. They may also be incorporated into various hallucinogenic drugs to potentiate their effect or for economic deception to stretch the supply of a true hallucinogen. Hallucinations occur in about 50% of the users; delirium and serious toxic symptoms are seen in only 25% of the users. Five deaths are known to have occurred due to impairment of judgement and physical coordination from the effects of stramonium containing asthma powders.
Electronic tagging of people with dementia
Authors: K. D Bail
Journal: BMJ (2003)

<b><i>Article abstract</i></b> The authors review the molecular genetics and pathophysiology of hereditary recurrent focal neuropathies: hereditary neuropathy with liability to pressure palsies (HNPP) and hereditary neuralgic amyotrophy (HNA). Significant progress in the understanding of HNPP and HNA has been achieved. HNPP and HNA are distinct clinical and pathologic disease entities with autosomal dominant inheritance. Molecular genetic studies have shown that HNPP and HNA are located on chromosome 17 but at distinct genetic loci (17p11.2 for HNPP, 17q25 for HNA). The 1.5 megabase deletion in 17p11.2 is the major cause of HNPP. This interstitial deletion causes the complete loss of one allele of the peripheral myelin protein 22 (<i>PMP22</i>) gene. Interestingly, rare HNPP patients are found without the 1.5 megabase deletion. However, these patients have distinct mutations in the <i>PMP22</i> gene resulting in altered expression of the <i>PMP22</i> protein. Current molecular genetic tests and clinical guidelines allow improved diagnosis, prognosis, and genetic counseling for patients with HNPP. Such tests are not available for HNA, because the disease-causing gene remains unknown. Molecular genetic advances in HNPP and HNA, as well as the study of transgenic animal and cellular models, will provide a more precise understanding of the disease mechanisms and will lead to the development of effective therapeutic tools for patients with inherited and sporadic recurrent peripheral neuropathies.
Cytologic Manifestations of Cervical and Vaginal Infections
Authors: Nancy B. Kiviat
Journal: JAMA (1985)

We used multiple logistic regression to analyze microbiological and clinical correlates of inflammatory and epithelial cell changes on Papanicolaou-stained cervical smears in patients from a sexually transmitted disease clinic. Among randomly selected patients, increased numbers of histiocytes and polymorphonuclear leukocytes and the presence of transformed lymphocytes were associated with<i>Chlamydia trachomatis</i>infection, while increased lymphocytes were associated with<i>Trichomonas vaginalis</i>infection; minimal squamous atypia was associated with yeast infection; and moderate squamous atypia and koilocytosis were associated with cervical condylomata visualized by colposcopy. Among patients referred for cervicitis,<i>C trachomatis</i>infection was also associated with reactive or atypical metaplastic cells. Distinct inclusions were seen by Papanicolaou smear in only 22% of<i>C trachomatis</i>infections. In randomly selected patients, however, the presence of transformed lymphocytes or increased histiocytes had a sensitivity of 95%, a specificity of 75%, and a positive predictive value of 50% in relation to isolation of<i>C trachomatis</i>, and could therefore be used for selection of patients for confirmatory testing for<i>C trachomatis</i>infection. (<i>JAMA</i>1985;253:989-996)
Synergism of Malnutrition and Infection
Authors: Nevin S. Scrimshaw
Journal: JAMA (1970)

Knowledge of human disease is acquired in three main ways: bedside study of the sick individual, laboratory experiment, and the epidemiological approach through observation of disease as it occurs in whole populations. All three, although first applied to infectious diseases, are equally applicable to nutritional disorders. In its simplest form the epidemiological method deals with the incidence and prevalence of a disease in various fractions of a population. The next step is to use these data to identify the multiple causative factors involved. This may be followed by the design and execution of field studies to test hypotheses of origin, and ultimately to evaluate suggested measures for prevention and control.<sup>1</sup> The epidemiological method requires an understanding of the ecology of a disease process as determined not only by a specific agent but also by environmental and host factors which usually play the larger role in determining occurrence and severity.